Melanoma of the Scalp Harboring a Novel AGFG1 :: ERBB4

ABSTRACT

ERBB4 (HER4) gain‐of‐function missense mutations have been implicated in cutaneous melanoma. In contrast, structural rearrangements involving ERBB4 are exceedingly rare. We describe a 59‐year‐old man with a rapidly enlarging 4.2‐cm melanoma of the scalp with high‐risk pathologic features, including epithelioid to plasmacytoid cytomorphology, ulceration, brisk mitotic activity, and microscopic satellitosis. RNA sequencing identified a novel in‐frame AGFG1 :: ERBB4 fusion joining AGFG1 exon 2 to ERBB4 exon 2. The ERBB4 portion retains the downstream coding sequence, including the tyrosine kinase domain. Concurrent molecular alterations included a pathogenic NF1 loss‐of‐function alteration, a TERT promoter mutation, CDK4 and STAT6 copy‐number gains, and TP53 copy‐number loss in a BRAF / NRAS / KIT ‐wild‐type background.